B. Bicalho, Juliana Marconi Giolo, S. Lilla
Jan 1, 2008
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Influential Citations
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Quality indicators
Journal
Biopharmaceutics & Drug Disposition
Abstract
Dihydroergotoxine is a mixture of semi‐synthetic ergot alkaloids mainly used for age‐related cognitive impairment. In this study, dihydroergotoxine (30 µM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy‐dihydroergocornine, hydroxy‐dihydroergocryptine and hydroxy‐dihydroergocristine on the basis of molecular mass measurements, determined with a time‐of‐flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy‐metabolites in human plasma by LC‐MS/MS after oral dosing of dihydroergotoxine mesylate (27 mg) to a healthy volunteer (male, age 45, height 1.93 m, weight 103 kg). In this preliminary approach, the peaks (Cmax) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04 µg/l. The peaks (Cmax) of their hydroxy‐metabolites were 0.98, 0.53 and 0.30 µg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy‐dihydroergocornine, hydroxy‐dihydroergocryptine and hydroxy‐dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma. Copyright © 2007 John Wiley & Sons, Ltd.